Bird-flu

Flown the coop

Controversial flu research is published

SOME said Ron Fouchier's work would help fend off a pandemic. Others called it a terrorist's cookbook. Authorities on either side of the Atlantic spent months examining the research. Now the rest of the world can read it, too. In a paper just published in Science, Dr Fouchier explains how bird flu might adapt to spread easily from person to person. The publication caps a long fight over whether the paper's benefits outweighed its risks. But this controversy will not be the last.

The prospect of a highly contagious H5N1 virus is scary. It can already hop nimbly from bird to bird, but is less acrobatic in humans. Some fear that if it ever adapted, the “Spanish flu” of 1918, which is reckoned to have killed as many as 100m people, could seem like a common cold by comparison. Of the 600 cases of H5N1 infection diagnosed since 2003, almost 60% have been lethal.

Dr Fouchier, of the Erasmus Medical Centre in the Netherlands, and Yoshihiro Kawaoka, of the University of Wisconsin-Madison, set out to learn which mutations might inspire H5N1 to speed from man to man. In December an American advisory board urged Science and Nature to publish redacted versions of their papers. After a self-imposed moratorium on research, opinion tilted towards full publication. It would, some argued, improve surveillance and speed the development of new drugs. Furthermore, publishing redacted work seemed impractical. By the end of April American and Dutch authorities had removed the last barriers to publication.

Dr Kawaoka's paper, the less controversial of the two, was published in May in Nature. Dr Kawaoka created a hybrid virus with H1N1, the strain that led to the 2009 outbreak. Just four mutations in an engineered version of haemagglutinin, the protein that helps H5N1 latch onto host cells, resulted in a virus that spreads easily from ferret to ferret (the human proxies in such tests). Dr Fouchier took a different approach. Most pandemics of the past century came from a mixing of animal and human flu viruses. Dr Fouchier wanted to understand whether H5N1 could become highly contagious without such mixing. The answer, his research suggests, is yes.

Three mutations are already known to make H5N1 more at home in human hosts. The first two, Q222L and G224S, modify haemagglutinin to help the virus attach to the surface of mammals' cells. The third mutation, E627K, makes the virus more likely to replicate. Dr Fouchier and his colleagues introduced the three mutations into an Indonesian strain of H5N1, then tested the virus in ferrets.

On its own, the mutated virus did little. Things got interesting when swabs were used to pass the virus from one ferret's nose to another's. After four such passages, the virus was better able to replicate. By the tenth it could spread through the air. The genomes of the viruses in each ferret had only five common mutations; the three introduced and two more, H103Y and T156A, which influenced haemagglutinin. The study was not all doom and gloom. None of the ferrets infected with the airborne virus died, and it seemed susceptible to drug treatment.

An accompanying paper in Science tries to estimate whether such mutations might appear simultaneously in nature. Better predictions will require more work. American regulators are trying to create a system to weigh the risks of similar research. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, hoped the World Health Organisation would discuss policies to oversee such research in July. But the meeting has been postponed. One controversy is over, but what comes next is as blurry as ever.